Філогенія білків-експортерів глікопептидних і деяких споріднених антибіотиків

Abstract

Glycopeptide antibiotics (GPAs) represent one of the most important classes of natural antibiotics coming from actinomycetes – high GC soil-dwelling Gram-positive bacteria. Among GPAs are important clinical compounds, such as vancomycin and teicoplanin, being “last defense line” against multidrug resistant Gram-positive pathogens. Recent works de­monstrated, that peptide antibiotics like ramoplanin and feglymycin, although having rather distinct structure, are genetically related to GPAs. Biosynthesis of all these compounds is coded within large gene assemblages – biosynthetic gene cluster (BGCs). BGCs of GPAs, ramoplanin, feglymycin and other related peptide antibiotics share multiple common features. One of them is the presence of genes coding for ABC-transporters. Most obvious role of these ABC-transporters is export of antibiotics. However, certain role of ABC-transporters in the auto-resistance cannot be excluded as well. Multiple genomes of actinomycetes were sequenced and are fully available today, allowing to build a significant collection of BGCs for GPAs and related peptide antibiotics. Therefore, in this work we aimed to investigate in silico distribution, structural features and phylogeny of ABC-transporters, encoded within 102 BGC of GPAs and related peptide antibiotics. We found out, that ABC-transporters from GPA BGCs are very similar to ABC-transporters from ramoplanin and feglymycin BGCs, as well as to ABC-transporters coded within BGCs of putative compounds. All these proteins belonged to MdlB(MsbA)-like ABC-transporters, possessing N-terminal transmembrane domain with 6 α-helices. Phylogenetic reconstruction revealed that these ABC-transporters fall into several clades, which might be correlated with specific types of peptide antibiotics. Finally, a wider phylogenetic reconstruction allowed to conclude the monophyly of ABC-transporters, encoded within BGCs of GPAs and other related peptide antibiotics.